Elimination of the immunogenicity of therapeutic antibodies.
The immunogenicity of therapeutic Abs limits their long-term use. The processes of complementarity-determining region grafting, resurfacing, and hyperchimerization diminish mAb immunogenicity by reducing the number of foreign residues. However, this does not prevent anti-idiotypic and anti-allotypic...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1999
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| _version_ | 1797050319798009856 |
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| author | Gilliland, L Walsh, L Frewin, MR Wise, M Tone, M Hale, G Kioussis, D Waldmann, H |
| author_facet | Gilliland, L Walsh, L Frewin, MR Wise, M Tone, M Hale, G Kioussis, D Waldmann, H |
| author_sort | Gilliland, L |
| collection | OXFORD |
| description | The immunogenicity of therapeutic Abs limits their long-term use. The processes of complementarity-determining region grafting, resurfacing, and hyperchimerization diminish mAb immunogenicity by reducing the number of foreign residues. However, this does not prevent anti-idiotypic and anti-allotypic responses following repeated administration of cell-binding Abs. Classical studies have demonstrated that monomeric human IgG is profoundly tolerogenic in a number of species. If cell-binding Abs could be converted into monomeric non-cell-binding tolerogens, then it should be possible to pretolerize patients to the therapeutic cell-binding form. We demonstrate that non-cell-binding minimal mutants of the anti-CD52 Ab CAMPATH-1H lose immunogenicity and can tolerize to the "wild-type" Ab in CD52-expressing transgenic mice. This finding could have utility in the long-term administration of therapeutic proteins to humans. |
| first_indexed | 2024-03-06T18:03:26Z |
| format | Journal article |
| id | oxford-uuid:0098fc57-366e-421c-9143-99df5c661f31 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:03:26Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:0098fc57-366e-421c-9143-99df5c661f312022-03-26T08:30:26ZElimination of the immunogenicity of therapeutic antibodies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0098fc57-366e-421c-9143-99df5c661f31EnglishSymplectic Elements at Oxford1999Gilliland, LWalsh, LFrewin, MRWise, MTone, MHale, GKioussis, DWaldmann, HThe immunogenicity of therapeutic Abs limits their long-term use. The processes of complementarity-determining region grafting, resurfacing, and hyperchimerization diminish mAb immunogenicity by reducing the number of foreign residues. However, this does not prevent anti-idiotypic and anti-allotypic responses following repeated administration of cell-binding Abs. Classical studies have demonstrated that monomeric human IgG is profoundly tolerogenic in a number of species. If cell-binding Abs could be converted into monomeric non-cell-binding tolerogens, then it should be possible to pretolerize patients to the therapeutic cell-binding form. We demonstrate that non-cell-binding minimal mutants of the anti-CD52 Ab CAMPATH-1H lose immunogenicity and can tolerize to the "wild-type" Ab in CD52-expressing transgenic mice. This finding could have utility in the long-term administration of therapeutic proteins to humans. |
| spellingShingle | Gilliland, L Walsh, L Frewin, MR Wise, M Tone, M Hale, G Kioussis, D Waldmann, H Elimination of the immunogenicity of therapeutic antibodies. |
| title | Elimination of the immunogenicity of therapeutic antibodies. |
| title_full | Elimination of the immunogenicity of therapeutic antibodies. |
| title_fullStr | Elimination of the immunogenicity of therapeutic antibodies. |
| title_full_unstemmed | Elimination of the immunogenicity of therapeutic antibodies. |
| title_short | Elimination of the immunogenicity of therapeutic antibodies. |
| title_sort | elimination of the immunogenicity of therapeutic antibodies |
| work_keys_str_mv | AT gillilandl eliminationoftheimmunogenicityoftherapeuticantibodies AT walshl eliminationoftheimmunogenicityoftherapeuticantibodies AT frewinmr eliminationoftheimmunogenicityoftherapeuticantibodies AT wisem eliminationoftheimmunogenicityoftherapeuticantibodies AT tonem eliminationoftheimmunogenicityoftherapeuticantibodies AT haleg eliminationoftheimmunogenicityoftherapeuticantibodies AT kioussisd eliminationoftheimmunogenicityoftherapeuticantibodies AT waldmannh eliminationoftheimmunogenicityoftherapeuticantibodies |